Low-density Lipoprotein - Medical Relevance

Medical Relevance

Because LDL particles can also transport cholesterol into the artery wall, retained there by arterial proteoglycans and attract macrophages that engulf the LDL particles and start the formation of plaques, increased levels are associated with atherosclerosis. Over time vulnerable plaques rupture, activate blood clotting and produce arterial stenosis, which if severe enough results in heart attack, stroke, and peripheral vascular disease symptoms and major debilitating events.

Increasing evidence has revealed that the concentration and size of the LDL particles more powerfully relates to the degree of atherosclerosis progression than the concentration of cholesterol contained within all the LDL particles. The healthiest pattern A, though relatively rare, is to have small numbers of large LDL particles and no small particles. Having small LDL particles, though common, is an unhealthy pattern B; high concentrations of small LDL particles (even though potentially carrying the same total cholesterol content as a low concentration of large particles) correlates with much faster growth of atheroma, progression of atherosclerosis and earlier and more severe cardiovascular disease events and death. This video, examining autopsy specimens from an actual heart attack resulting in sudden death, shows the seqence. These videos, and, illustrate the sequence of events and why, though the underlying process develops over decades, the symptoms are often of sudden onset.

LDL particles are formed as VLDL lipoproteins lose triglyceride through the action of lipoprotein lipase (LPL) and they become smaller and denser (i.e. fewer fat molecules with same protein transport shell), containing a higher proportion of cholesterol esters .

A hereditary form of high LDL is familial hypercholesterolemia (FH). Increased LDL is termed hyperlipoproteinemia type II (after the dated Fredrickson classification).

LDL particles pose a risk for cardiovascular disease when they invade the endothelium and become oxidized, since the oxidized forms are more easily retained by the proteoglycans. A complex set of biochemical reactions regulates the oxidation of LDL particles, chiefly stimulated by presence of necrotic cell debries and free radicals in the endothelium.